Simple Blood Test Can Now Diagnose De Vivo Disease

Glut1 deficiency syndrome, a neurological disorder caused by a genetic mutation that causes a lack of glucose in the brain, can cause seizures, abnormal movements and developmental delays. Scientists have developed a blood test called METAGlut1 that can quickly diagnose the disease without the need for an invasive lumbar puncture, with a sensitivity of around 80% and a specificity of over 99%.

Glut1 deficiency syndrome is a relatively little-known neurological disease, despite its debilitating consequences that remain unknown to the medical community. The disease is caused by a mutation in the SLC2A1 gene, which causes a violation of the glucose transporter GLUT1 in patients. Because this transporter plays an important role in facilitating the uptake of glucose by glial cells, its damage deprives the brain of the sugar it needs to function properly. As a result, patients experience seizures, episodes of unusual movements, and developmental delays.

However, adverse symptoms can be reduced by managing the metabolic disorders that cause the disease by following a high-fat ketogenic diet. In addition, promising new therapeutic molecules designed to compensate for the deficiency in glucose delivery to brain cells are being evaluated. "Undiagnosed patients suffer from missed opportunities. They can be cured, said Professor Fanny Mauchel, the study's lead researcher. Better identification is urgent, because many are missing or are diagnosed too late."

The incidence of Glut1 deficiency syndrome in the general population is estimated to be 1 in 24,000. These data may be underestimated if only patients with epilepsy are considered, rather than patients with isolated and non-specific symptoms such as learning difficulties or abnormal movements. The diagnosis is even more difficult, as it was based on a lumbar puncture supplemented with genetic testing.

"These invasive procedures, which are often time-consuming and costly, significantly limit access to treatment," the researchers added. Hence the interest in the search for blood biomarkers that can quickly diagnose Glut1 deficiency syndrome".

Red blood cells are full of clues

In fact, the transporter GLUT1 is not only present in the brain's endothelial and glial cells, but also binds to the surface of erythrocytes, in red blood cells. The diagnostic test developed by Paris METAFORA medtech biosystems allows the measurement of GLUT1 on its surface using flow cytometry, a technique commonly used in analytical laboratories. A simple blood draw is required for the test without taking the patient on an empty stomach. Results are available in 48-72 hours.

To test the new METAGlut1 test, the AP-HP group and 33 French clinical research centers led by Professor Fanny Moschel recruited 549 patients in the prospective cohort, that is, people with suspected disease, and 87 patients in the retrospective cohort. . already diagnosed cohort. Goals, goals? Compare the performance and accuracy of METAGlut1 with reference diagnostic tests that require CSF sampling and genetic analysis.

The researchers' results show that METAGlut1 has a sensitivity of about 80%, a specificity of over 99% and a high predictive value comparable to a reference test. "These data allow us to officially confirm the benefits of the test," says Professor Fanny Mochel. This will allow a quick and easy search for Glut1 deficiency syndrome in many patients. With positive results, treatment can be started immediately, which significantly improves the prognosis, especially in children with full brain development.

Therefore, the study authors recommend testing all children over 3 months of age and adults with mental retardation, neurodevelopmental disorders, movement abnormalities, or epilepsy, especially if they are drug-resistant and on a ketogenic diet. In fact, when used in the early symptomatic phase, METAGlut1 can immediately identify 80% of patients with Glut1 deficiency syndrome. Therefore, the French National Health Authority recommended its replacement, paving the way for its introduction in Europe and the United States.

References: "Prospective multicenter validation of a single blood test for the diagnosis of Glut1 deficiency syndrome" Fanny Moschel, Domitil Gras, Marie-Pierre Luton, Manon Nizu, Donatella Giovannini, Caroline Delattre, Melody Obart, Magali Barth, Anne de Saint-Martin, Diane Dumart , Nouha Essid, Alexa Garros, Caroline Ashon Le Camus, Celia Hoebeke, Sylvie Nguyen Tich, Maximilian Perivier, Serge Rivera, Anne Rolland, Agatha Ruberty, Catherine Sarre, Caroline Sevin, Dorothy Wieel, Marc Sitbon, Jean-Marc Costa , Roser Pons , Angels Garcia-Cazorla, Sandrine Vuillaume, Vincent Petit, Odile Boespflug-Tanguy, and Darryl S. De Vivo, for the MetaGlut1 Research Group, April 19, 2023, Neurology .
DOI: 10.1212/WNL.0000000000207296

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